Nitric oxide (NO) mediates bactericidal and tumoricidal actions of macrophages (J. B. Hibbs et al., J. Immunol. 138:550 (1987); J. B. Hibbs et al., Biochem. Biophys. Res. Commun. 157:87 (1988); C. F. Nathan et al., Curr. Opin. Immunol. 3:65 (1991)) and blood vessel relaxation of endothelial cells (R. F. Furchgott et al., Nature 288:373 (1980); S. Moncada et al., Biochem, Pharmacol. 38:1709 (1989); R. M. Palmer, et al., Nature 327:524 (1987); R. F. Furchgott et al., FASEB J. 3:2007 (1988); L. J. Ignarro, Annu. Rev. Pharmacol. Toxicol. 30:535 (1990)). NO also is likely a major neuronal messenger (D. S. Bredt et al., Neuron 8:3 (1992); J. Garthwaite, Trends Neurosci. 14:60 (1991)). Immunohistochemical studies localize NO synthase (NOS) to neurons in the brain as well as to discrete populations of autonomic nerves in the periphery (D. S. Bredt et al., Nature 347:768 (1990)), where NO fulfills most characteristics of a neurotransmitter. For instance, NOS is highly localized to cell bodies and fibers of the myenteric plexus of the gastrointestinal pathway (Bredt, et al., supra; Garthwaite, supra). The non-adrenergic, noncholinergic relaxation evoked by physiologic stimulation of myenteric plexus neurons is potently and selectively blocked by NOS inhibitors (K. M. Desai et al., Nature 351:477 (1991); T. M. Cocks et al., Naunyn Schmiedebergs Arch. Pharmacol. 341:364 (1990); A. Tttrup et al., Am. J. Physiol. 260:G385 (1991); H. Bult et al., Nature 345:346 (1990); J. S. Gillespie et al., Br. J. Pharmacol. 98:1080 (1989); M. V. Ramagopal et al., Euro. J. Pharmacol. 174:297 (1989); A. Gibson et al., Br. J. Pharmacol. 99:602 (1990).
Penile erection is thought to involve parasympathetic, neuronally mediated relaxation of the blood vessels as well as of the trabecular meshwork of smooth muscle comprising the corpora cavernosa (R. Blanco et al., Am. J. Physiol. 254:468 (1988)). The neuronal chemical mediator of erection has not been established. Vasoactive intestinal polypeptide (VIP) occurs in limited populations of nerve fibers in the penis (J. M. Polak, Lancet 2:217 (1981); E. A. Willis et al., Life Sci. 33:383 (1983)), but direct administration of VIP does not fully mimic physiologic erection (E. A. Kiely et al., Br. J. Urol. 64:191 (1989); J. B. Roy et al., J. Urol. 143:302 (1990); K. P. Juenemann, et al, J. Urol. 138:871 (1987); W. D. Steers et al., J. Urol. 132:1048 (1984).). In isolated smooth muscle from the corpus cavernosum of several species, relaxation evoked by electrical field stimulation could be blocked by NOS inhibitors in some studies (R. S. Pickard et al., Br. J. Pharmacol. 104:755 (1991); L. J. Ignarro et al., Biochem. Biophys. Res. Commun. 170:843 (1990); N. Kim et al., J. Clin. Invest. 88:112 (1991); F. Holmquist et al., Acta Physiol. Scan. 141:441 (1991); J. Rajfer et al., New Eng. J. Med. 326:90 (1992) but not in others (J. S. Gillespie et al., Br. J. Pharmacol. 97:453P (1989); N. O. Sjostrand et al., Acta. Physiol. Scan. 140:297 (1990). Blockade of relaxation of isolated smooth muscle by NOS inhibitors can establish NO as a mediator of cavernosal muscle relaxation but does not permit conclusions as to whether it is a neuronal, transmitter-like messenger or whether it can mediate a physiologic erection in an intact body. There is a need in the art for methods of inducing erections in males who are now incapable of achieving them. There is also a need in the art for methods of relieving erections which are not associated with sexual arousal or desire.